Mehandru Saurabh, Deren Sherry, Kang Sung-Yeon, Banfield Angela, Garg Aakash, Garmon Donald, LaMar Melissa, Evering Teresa H, Markowitz Martin
Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, New York, USA.
Center for Drug Use and HIV Research, New York University College of Nursing, New York, USA.
J Addict Res Ther. 2015;6(4):1-8. doi: 10.4172/2155-6105.1000257.
Injection drug use (IDU) remains a major risk factor for HIV-1 acquisition. The complex interplay between drug use, non-sterile injection, and Hepatitis C remains poorly understood. We conducted a pilot study to determine the effect of IDU on immune parameters among HIV-uninfected and -infected individuals. We hypothesized that IDU could further augment immunological changes associated with HIV-1 infection, which could in turn affect HIV pathogenesis.
HIV-uninfected and -infected subjects with IDU, and non-IDU controls were recruited to obtain socio-demographic and drug-related behaviours. Blood (PBMC) and mucosal (MMC) mononuclear cells were analysed for cellular markers of immune activation (CD38 and Ki67). Serum ELISA was performed to determine levels of soluble CD14, a marker of immune activation.
No significant quantitative differences in CD4 and CD8 T cell levels were observed between IDU and non-IDU subjects when accounting for the presence of HIV-1 infection. However, increased levels of cellular and soluble markers of immune activation were documented in cells and plasma of HIV-uninfected IDU subjects compared to non-injectors. Additionally, sharing of injection paraphernalia was related to immune activation among HIV-uninfected IDU subjects.
IDU, with or without HIV-1 infection, results in a significant increase in immune activation in both the peripheral blood and the GI tract. This may have significant impact on HIV transmission, pathogenesis, and immunologic responses to combination antiviral therapy. This study provides compelling preliminary results which in turn support larger studies to better define the relationship between IDU, infection with HIV-1, co-infection with Hepatitis C and immunity.
注射吸毒仍是感染HIV-1的主要危险因素。吸毒、非无菌注射与丙型肝炎之间复杂的相互作用仍未得到充分理解。我们开展了一项试点研究,以确定注射吸毒对未感染和已感染HIV个体免疫参数的影响。我们假设注射吸毒会进一步加剧与HIV-1感染相关的免疫变化,进而影响HIV发病机制。
招募有注射吸毒史的未感染和已感染HIV的受试者以及无注射吸毒史的对照者,以获取社会人口统计学和与毒品相关的行为信息。分析血液(外周血单核细胞)和黏膜(黏膜单核细胞)中的免疫激活细胞标志物(CD38和Ki67)。进行血清ELISA检测以确定可溶性CD14水平,其为免疫激活标志物。
在考虑HIV-1感染情况时,注射吸毒者与非注射吸毒者之间未观察到CD4和CD8 T细胞水平有显著的定量差异。然而,与非注射吸毒者相比,未感染HIV的注射吸毒者的细胞和血浆中免疫激活的细胞和可溶性标志物水平有所升高。此外,共用注射器具与未感染HIV的注射吸毒者的免疫激活有关。
无论是否感染HIV-1,注射吸毒都会导致外周血和胃肠道的免疫激活显著增加。这可能对HIV传播、发病机制以及对抗病毒联合疗法的免疫反应产生重大影响。本研究提供了令人信服的初步结果,进而支持开展更大规模的研究,以更好地界定注射吸毒、HIV-1感染、丙型肝炎合并感染与免疫之间的关系。